Reduced Loss Of Bone Mineral Density Research Articles

SAT-539 The Utility of Prophylactic Zoledronic Acid in Patients Undergoing Lung Transplantation: A Retrospective Analysis

Purpose Osteoporosis is prevalent among lung transplant candidates and exacerbated post-transplant by immunosuppressive therapy (glucocorticoids and calcineurin inhibitors). Many groups, ours included, prophylactically treat lung transplant recipients with bisphosphonate therapy to prevent bone mineral density (BMD) loss and reduce fracture rates. However, no documented national or international consensus protocols exist to date. Given the early and dose-related fracture increase seen with glucocorticoids, our protocol comprises 6-monthly intravenous zoledronic acid (ZA) from wait-listing to 1 year post-transplant, with interval reassessment to guide ongoing treatment. Use of ZA to protect bone health in transplant recipients has been tested and proven efficacious in liver and bone marrow transplantation, however, its effect in the lung transplant population has not previously been described in the literature. The purpose of our study is to audit the impact of this protocol on BMD and fracture occurrence in lung transplant patients. Methods A retrospective analysis was performed on all adult lung transplant recipients between April 2012 and October 2014. 60 of 142 met inclusion criteria, which included a 3-year follow up period post-transplant with BMD assessment 1) within 24 months pre-transplant and 2) 36-60 months post-transplant. Those who received ZA within 6 months of their transplant as per protocol (n=37) were compared to those who did not (n=23). The outcome measures were change in BMD at the lumbar spine and hip (primary), and fracture occurrence (secondary). Results Primarily due to a non-uniform referral system, 61.7% of patients received ZA as per protocol. The median baseline BMD (g/cm2) in this group was 0.99 (IQR: 0.90-1.08) at the spine and 0.80 (IQR: 0.71-0.93) at the femur, while the non-protocol group had a baseline BMD of 1.08 (IQR:0.99-1.13) and 0.88 (IQR:0.81-0.92), respectively. The protocol treated group experienced a median change in BMD of 8.1% (IQR:-2.8%-10.8%) at the spine and 1.4% (IQR:-4.1%-7.4%) at the femur, compared to -1.2% (IQR:-5.2%-5.9%) and -3.9% (IQR:-8.6%-2.8%), respectively, in the non-protocol group (p=0.003). In the protocol treated group, 6 (16.2%) patients suffered an atraumatic fracture, compared to 7 (30.4%) in the non-protocol group (p=0.22). Fractures in traditional osteoporotic sites accounted for 3 (8.1%) and 5 (21.7%) of these, in the two groups respectively (p=0.24). Despite improvement in BMD there was no significant difference seen in fracture rates, likely due to cohort size. Conclusion Our results suggest that prophylactic ZA in the lung transplant cohort is effective in reducing BMD loss and may reduce fracture rates. Proven benefit of this protocol may influence clinical practice not only at our center but may contribute to an international consensus on the best management of bone health in lung transplant patients.

The Utility of Prophylactic Zoledronic Acid in Patients Undergoing Lung Transplantation - A Retrospective Analysis

Purpose Osteoporosis is prevalent among lung transplant candidates and is exacerbated post-transplant by immunosuppressive therapy (glucocorticoids and calcineurin inhibitors). Osteoporotic fractures are a significant source of morbidity. Low bone mineral density (BMD) is a well-recognised surrogate for fracture risk. Intravenous zoledronic acid (ZA) effectively prevents the former and reduces the latter in post-menopausal osteoporosis. Many groups, ours included, prophylactically treat lung transplant recipients with bisphosphonates to prevent BMD reduction and reduce fracture rates. However, no documented national or international consensus exists to date. Our protocol comprises six-monthly ZA infusions from wait-listing, with interval reassessment to guide ongoing treatment. The purpose of our study is to audit the impact of this protocol on BMD and fracture occurrence. Methods A retrospective analysis was performed on all adults receiving a lung transplant from April 2012 to October 2014. 60 of 142 met inclusion criteria, which included a 3-year follow up period post-transplant with BMD assessment 1) within 24 months pre-transplant and 2) 36-60 months post-transplant. Those who received ZA within 6 months of their transplant as per protocol (n=37) were compared to those who did not (n=23). The outcome measures were change in BMD at the lumbar spine and hip (primary), and fracture occurrence (secondary). Results The group treated as per protocol experienced a median change in BMD of 8.11% at the spine and 1.39% at the femur, compared to -1.20% and -2.92%, respectively, in the group not treated as per protocol (p=0.003) (table 1). Our results suggest that prophylactic ZA in the lung transplant cohort is effective in reducing BMD loss and may reduce fracture rates. Conclusion Proven benefit of this protocol may influence clinical practice not only at our centre but may contribute to an international consensus on the best management of bone health in lung transplant patients.

Association of intact parathyroid hormone levels with subsequent hip BMD loss: the Osteoporotic Fractures in Men (MrOS) Study.

There is little information on the association between intact PTH (iPTH) and longitudinal changes in bone mineral density (BMD) in older men. This association was evaluated in relation to conditions related to higher iPTH [e.g. decreased renal function, low serum 25-hydroxyvitamin D (25[OH]D)]. Eligible men were part of a random sample of 1593 community-dwelling individuals aged 65 yr or older participating in the Osteoporotic Fractures in Men study with baseline iPTH data. Of these, 1227 had at least two BMD measurements at the total hip and femoral neck over a mean follow-up of 4.5 yr. Annualized BMD change across iPTH quartiles was estimated using mixed-effects regression models, adjusting for age, serum calcium, serum 25(OH)D, estimated glomerular filtration rate, and other factors. Splines were used to identify more optimal iPTH thresholds associated with less BMD loss. Among the cohort of 1138 eligible men, men in the highest quartile of iPTH (≥38 pg/ml) lost 0.46% per year at the total hip compared with men in the lowest iPTH quartile who lost 0.22% per year (P = 0.0004). Results were similar at the femoral neck. The association between iPTH and BMD loss was not modified by baseline estimated glomerular filtration rate or 25(OH)D status. Spline results suggested that iPTH levels below 30 pg/ml were more physiologically optimal than higher iPTH values in reducing BMD loss, although an exact threshold for optimal iPTH was not identified. Older men with higher iPTH levels had approximately a 2-fold greater rate of BMD loss compared with men with lower iPTH levels, irrespective of estimated glomerular filtration rate and 25(OH)D.

Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss.

Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss. The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss. This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial. The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ). Participants included 186 postmenopausal women aged 40-65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to -2.5. Women, stratified by lumbar T-score (<-1.50 and >or=-1.50) and years since menopause (<or=5 and >5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements. BMD was measured at 6 months and annually by dual-energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content, and height were secondary outcomes. After 36 months of therapy, changes of -2.1% in the active group (n = 88) and -2.5% in the placebo group (n = 82) in lumbar spine BMD were seen (P = 0.59; 95% confidence interval -1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P < 0.001). Other adverse and serious adverse events were not different. BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only approximately 16 mg/d); a sub-therapeutic dose.

Treatment of Osteoporosis/Osteopenia in Pediatric Leukemia and Lymphoma

To evaluate the efficacy and safety of various treatment options for osteopenia and osteoporosis secondary to cancer treatment in pediatric patients undergoing cancer therapy. A systematic search of PubMed (1949-November 2008) and International Pharmaceutical Abstracts (to November 2008) was conducted using the following search terms: osteoporosis, osteopenia, pediatrics, cancer, neoplasms, chemotherapy, bisphosphonates, calcium, vitamin D, calcitonin, and physical therapy. All prospective studies that evaluated various osteoporosis treatment options in pediatric patients undergoing chemotherapy were included. Results from studies evaluating bisphosphonates and other treatments in children with osteoporosis due to other causes were also included if important safety and efficacy data were provided. Most commonly reported primary efficacy endpoints included comparisons of bone density parameters measured before and after treatment. Four clinical studies and 2 case reports describing treatment with bisphosphonates, specifically alendronate and pamidronate, for osteoporosis or osteopenia in pediatric cancer patients were identified. Results from the trials showed that these medications were efficacious in reducing bone mineral density loss during cancer therapy and were well tolerated in this special population. Primary efficacy endpoints included improvements in Z-scores measured by dual-energy X-ray absorptiometry scans. The most commonly reported adverse effects included hypocalcemia, mild stomach upset, and infusion-related hyperpyrexia. Four additional clinical trials involving the treatment of osteoporosis or osteopenia in children and adolescents who developed bone degeneration after chronic steroid therapy are also included. In these trials, treatment options such as calcitonin, and calcium and vitamin D supplementation were also shown to be beneficial. The clinical trials published to date are limited to only a few conducted in small populations of patients diagnosed with lymphoblastic leukemia or non-Hodgkin's lymphoma. However, alendronate and pamidronate both appeared to be effective options in improving bone mineral density scores with minimal adverse effects.